• Test code: 08141
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Epidermodysplasia Verruciformis Panel

Test description

The Invitae Epidermodysplasia Verruciformis Panel analyzes 4 genes that are associated with epidermodysplasia verruciformis (EV) and has also been referred to as Lewandowsky-Lutz dysplasia. This test is useful for the diagnosis of patients who are suspected of having EV from clinical symptoms and laboratory findings, including characteristic skin lesions primarily on the face, neck, trunk, and extremities, non-melanoma skin cancers, as well as extreme susceptibility to some human papillomavirus (HPV) infection. Genetic testing of the genes in this panel may confirm a diagnosis and help guide treatment and management decisions.

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Primary panel (4 genes)

Gene Disorder Protein name Protein symbol
CXCR4 WHIM (warts, hypogammaglo- bulinemia, infections, myelokathexis) syndrome Chemokine, CXC motif, receptor 4 CXCR4
RHOH T-cell immunodeficiency with epidermodysplasia verruciformis ras homolog gene family member H RHOH
TMC6 EVER1 deficiency EVER1 EVER1
TMC8 EVER2 deficiency EVER2 EVER2

Epidermodysplasia verruciformis (EV) is a rare, inherited disorder characterized by chronic persistent infection with human papillomavirus (HPV) and association with increased risk of skin carcinoma. In affected individuals, widespread skin eruptions of flat-to-papillomatous, wart-like lesions and reddish-brown pigmented plaques appear mainly on the sun-exposed area, but may be generalized involving all parts of body. Skin tumors (carcinomas), especially squamous cell carcinoma (in situ or invasive), occur in about 30–70% cases and typically start between the ages of 20 and 40 years, but metastasis is uncommon.

EV patients usually have lesions that are infected with multiple types of HPV, most specifically the EV-HPV types (including HPV 4, 5a, 5b, 8, 9, 12, 14, 15, 17, 19-25, 36-38, 47, 50). HPV types 5, 8, and 14d have been isolated in more than 90% of EV patients with squamous cell carcinoma, and are most commonly associated with malignant transformation of EV.

TMC6 and TMC8 are the two most commonly described causative genes for EV (together they account for roughly 75% of EV patients). The other causes of EV are rare.

The most common cause of EV is inherited in an autosomal recessive manner, but sex-linked and autosomal dominant inheritance patterns have also been reported.

WHIM syndrome is usually transmitted as an autosomal dominant trait, but autosomal recessive or sporadic cases have also been reported.

Epidermodysplasia verruciformis is individually rare, with a prevalence of less than 1 in 1,000,000. A little more than 200 cases have been reported in the literature so far.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CXCR4 NM_003467.2
RHOH NM_004310.4
TMC6 NM_007267.7
TMC8 NM_152468.4